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Many excipients are extracted from or purified using organic solvents. These solvents are normally removed by drying. It is important that excipient specifications include tests and limits for solvent residues.

8.2.4.7 Stability While many excipient products are stable and may not require extensive testing to assure stability, the stability of excipients is an important factor contributing to the overall quality of the drug product. For excipients that have been on the market for a long time historical data may be used to indicate stability.

Where historical data do not exist a documented testing and/or evaluation program designed to assess the stability characteristics of the excipient should be undertaken. The results of such stability testing and/or evaluation should be used in determining appropriate storage conditions and retest or expiry dates. The testing program should include the following:

  • the number of batches, sample sizes and test intervals,

  • storage conditions for samples retained for testing,

  • suitable stability-indicating test methods,

  • storage of the excipient in containers that simulate the market container,

where possible. The stability of excipients may be affected by undetected changes in raw materials or subtle changes in manufacturing procedures or storage conditions. Excipients may also be shipped in a variety of packaging types that can affect their stability (for example plastic or glass bottles, metal or plastic drums, bags, tank cars or other bulk containers, etc.).

Some excipients may be available in different grades (for example various molecular weights of a polymer or different monomer ratios, different particle sizes, bulk densities etc.) or may be mixtures of other excipients. These excipients may be very similar to others within a product group. Minor quantitative differences of some of the components may be the only significant variation from one product to another. For these types of excipients, a “model product” approach may be appropriate to assess the stability of similar excipients. Stability studies of this type should involve selection of several “model products” that would be expected to simulate the stability of the product group being assessed. This selection should be scientifically sound and documented. Data from stability studies of these “model products” can be used to determine theoretical stability for similar products.

8.2.4.8 Expiry/Retest Periods An expiry or retest period should be assigned to each excipient and communicated to the customer. Common practice is to use a retest period, rather than an expiry period.

8.3 Control of Nonconforming Product

Raw material, intermediate or finished excipient found not to meet its specification should be clearly identified and controlled to prevent inadvertent use or release for sale. A record of nonconforming product should be maintained. Incidences of non-conformance should be investigated to identify the cause. The investigation should be documented and action taken to prevent recurrence.

Copyright © 2006 The International Pharmaceutical Excipients Council and Copyright © 2006 Pharmaceutical Quality Group

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